This application is filed pursuant to 35 U.S.C. xc2xa7371 as a United States National Phase Application of International Application No. PCT/EP99/09685 filed Dec. 9, 1999, which claims priority from GB9827200.8 filed Dec. 11, 1998.
The present invention relates to a dry powder delivery device, and in particular to a dry powder delivery device which has application in dry powder inhalers for delivering to a patient a metered dose of a pharmaceutical substance formulated in powder form.
Delivery of therapeutic, prophylactic and diagnostic agents to the lungs of a patient may be accomplished using a variety of inhaler devices. One class of dry powder inhalers includes reservoir based dry powder systems. Reservoir based inhalers contain a bulk reservoir of a bioactive (therapeutic, prophylactic or diagnostic) agent suitable for inhalation, a mechanism for metering the bulk powder into individual doses, and a mechanism for aerosolising the dry powder into a patient""s inhalation pathway for delivery to the lungs.
Reservoir based dry powder inhalers must operate within the constraints afforded by the use of bulk dry powders. For example, powders used within typical dry powder inhalers do not flow perfectly and always have a degree of cohesiveness. Thus, great care must be taken to ensure that powder flows within the device in order to assure that the powder reaches the appropriate point where it is metered. This is typically accomplished by blending the powder with an excipient, which is less cohesive and which allows the powder to flow. Excipients also act to dilute the active agent within the powder blend to allow more precise metering of potent active agents in an appropriate dose. Although excipients have several beneficial effects in terms of powder flow and metering, as a general rule, delivery of non-critical material is to be avoided. Thus, where possible, the better practice is to reduce the amount of non-essential excipient in a blend.
The flow of powders within inhaler devices may be effected by other mechanisms. For example, the movement of powder through a device to make it available for metering into doses may be assisted by applying a load to the powder within the reservoir. Such a load may be applied with a spring-biased plunger exerting pressure on the powder. The load biases movement of the powder towards the dosing mechanism in the device. This load mechanism can, however, create a compacting effect in the powder. The compacted powder may xe2x80x9cbridgexe2x80x9d at or near the dosing mechanism and therefore no longer flow as desired. Thus, it is desirable to avoid powder bridging.
An important consideration in a reservoir based dry powder inhaler is how the inhaler assures the accurate metering of the bioactive agent into doses, and assuring that this metering can be uniformly repeated within tight tolerances. In a reservoir based system, over-compaction of a therapeutic powder while metering a given dose or delivering multiple doses of powder to a patient where a single dose is intended may lead to an overdose. Depending on the agent being metered, an overdose may cause serious adverse side effects. Likewise, partial delivery or non-delivery of a dose of medication to a patient may fail to provide the desired therapeutic effect, also leading to potentially life-threatening situations, depending upon the condition being treated.
Reservoir based dry powder inhalers are well known in the art. For example, WO 92/18188 and WO 93/03782 disclose inhalers including powder reservoirs containing a pharmaceutical substance, generally combined with a powdered bulking agent. A dosing rod or shaft is moved within the reservoir in order to fill a metering recess therein. The rod or shaft is then pulled out of the reservoir in order to deliver the metered dose to an inhalation channel, where the dose can then be inhaled by the patient.
WO 92/04928 discloses an alternative reservoir based inhaler system in which the metering mechanism relies on a worm or auger positioned coaxially with the axis of the reservoir. A plunger in the device biases powder toward the end of the worm. The worm pushes out a xe2x80x9cfingerxe2x80x9d of compacted powder at its opposite end that is then cut off at the end of a complete rotation. This xe2x80x9cfingerxe2x80x9d provides the metered dose. Although the reference asserts that doses of precise size are delivered, there appears to be nothing to prevent the worm being repeatedly turned so that the patient could inhale a plurality of doses in a single inhalation. Moreover, the parallel and co-axial position of the worm within the reservoir potentially yields waste, due to the fact that when the coaxially aligned plunger abuts the end of the worm, it no longer biases the powder toward the auger. The remaining powder is no longer available for delivery to the patient, thus shortening the useful life of the device.
In contrast to the prior art devices, the aim of the present invention is to directly address the powder flow, powder content, dose accuracy and reproducibility concerns required for reservoir based dry powder systems. The present invention provides a novel metering system for dry powders having application in the area dry powder inhalers. In particular, the present invention provides a metering system for use in hand-held, dry powder reservoir based inhalers. The metering system may also be used in any instance where the accurate and reproducible metering of powders is desirable.
The present invention provides a dry powder metering system usable in dry powder inhalers comprising a housing, which has a walled portion defining a reservoir containing a powder. A bore intersects the reservoir at one end. A fluted auger positioned in the bore permits the transfer of powder through the bore. The auger communicates with a bore egress, where the powder is passed to a recess in a dosing member positioned adjacent to the bore egress. The dosing member recess is of a desired volume and the dosing member is moveable between a loading position adjacent the bore egress and a delivery position where the powder may be delivered.
The orientation of the reservoir to the auger within the bore is non-coaxial and non-parallel. Preferably, the axis of the reservoir is transverse to the axis of the auger, for example at approximately 90 degrees, with the reservoir only opening on to a portion of the cylindrical surface area of the auger, e.g. 50% or less than 50% of that surface area.
The auger and bore egress are designed such that rotation of the auger transfers powder into the dosing recess, but excessive rotation does not compact the powder at the dosing recess. The delivery of the powder to the recess may be made more reliable by increasing the volume of the bore egress to form an intermediate chamber. The intermediate chamber, which is later described in reference to the preferred embodiment, may act to even out cavitation within the powder and reduce the likelihood that dead space would be created within the dosing recess.
Thus, the present invention relates to a powder delivery device comprising a housing defining a reservoir, a bore and a bore egress, the reservoir having a top and a bottom and an axis therebetween. The bore extends into the housing from a bore egress, and the bore and the reservoir intersect at a bore/reservoir interface. The bore has an axis, which is non-parallel and non-coaxial with the axis of the reservoir. A rotatable auger is positioned coaxially within the bore. The auger has a spiral flute extending between the bore/reservoir interface and the bore egress. The delivery device may also have a dosing plate having a dosing recess for metering powder transferred from the bore egress.
The present invention also relates to a dry powder inhaler apparatus having an inhaler body with an air inlet, an air outlet, and an air flow pathway therebetween. The inhaler further comprises a walled portion defining a reservoir and a bore, the reservoir having first and second ends and an axis therebetween, the bore extending from a bore egress into the housing. The bore and the reservoir are in communication at one end of the reservoir at a bore/reservoir interface. The bore has an axis and the bore axis is non-parallel and non-coaxial with the axis of the reservoir. A rotatable auger is positioned coaxially within the bore. A spiral groove is defined in the auger. and the groove extends between the bore/reservoir interface and the bore egress. The inhaler also has a dose plate that has defined within it a dosing recess. The dose plate is movable between a loading position in which the dosing recess is in communication with the bore egress and a delivery position in which the dosing recess is in communication with the air flow pathway.
Additionally, the present invention relates to a method of delivering a powder to the respiratory tract of a patient comprising:
a. providing a dry powder inhaler having an air inlet, an air outlet and an air flow pathway defined therebetween, the inhaler further comprising:
(i) a housing defining a reservoir and a bore, the reservoir having a top, a bottom and an axis therebetween, the bore extending from a bore egress into the housing, the bore and the reservoir in communication at the bottom of the reservoir at a bore/reservoir interface, the bore having an axis, the axis of the bore being non-parallel and non-co-axial with the axis of the reservoir;
(ii) a powder positioned within the reservoir;
(iii) an auger positioned within the bore, the auger being coaxialy rotatable within the bore, the auger having a spiral groove defined therein, the groove extending between the bore/reservoir interface and the bore egress;
(iv) a dose plate defining a dosing recess, the dosing recess positioned adjacent the bore egress, the dosing recess exposable to the airflow pathway; and
b. rotating the auger to transport the powder from the reservoir into the auger groove and to the dosing recess.
c. Exposing the dosing recess to airflow pathway;
d. Creating an airflow in the airflow pathway; and
e. Entraining the powder contents of the dosing recess into the airflow to deliver the powder to the patient.
Thus, the present invention is based on the surprising realisation that bridging of powders may be reduced or avoided in a delivery device having an auger interfacing a reservoir in a non-parallel fashion. Thus orientation also allows the reservoir to be emptied of powder, thus minimising powder waste and maximising the useful life of the device. The orientation of the auger and reduction of potential bridging locations may also yield a benefit in permitting accurate delivery of less flowable powders, thus potentially allowing the use of powder blends with reduced course excipient to drug ratios.
Additionally, the present invention is based on the surprising realisation that an auger could be used to feed powder from a reservoir towards a dosing recess, with the amount of active agent metered remaining constant, regardless of the number of times the auger is rotated after the appropriate dose has been metered. It was to be expected that excessive turning of the auger would force powder from the reservoir towards the dosing recess and thus lead to an over compaction of the powder at that point. Surprisingly, however, it has been found by the inventors that the powder slips on itself, and that the dosing recess can reliably deliver a metered dose with only a predetermined minimum rotation of the auger. Accurate metering is thus not affected by excessive rotation of the auger.
Further still, the present invention is based on the surprising realisation that the inclusion of an intermediate chamber at the bore egress is useful in evening out cavitation and reducing dead space in a dosing recess, thus yielding a more even dosing of a metered powder.
These and other intentions and advantages will become apparent in the disclosure provided herein.